Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation

Chen, Fan; Chen, Dandan; Zhao, Xinmei; Sm, Yang; Li, Zhe; Sanchı́s, Daniel; Jin, Liang; Qiang, Xizhe; Wang, Kaiye; Xu, Yitao; Zhang, Yubin; Ye, Junmei

doi:10.1016/j.bbadis.2017.08.022

Cited by 30 publications

(27 citation statements)

References 64 publications

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“…In a good connection with our histopathological findings, Chen et al [26] speculated that HFD rats exhibited cardiac fibrosis and enhanced lipid accumulation and inflammation without affecting cardiac morphology in the heart of rat, supposing that interleukin (IL)-6 engages to regulate lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation, and myocardium lipotoxicity during obesity induced by HFD.…”

Section: Discussionsupporting

confidence: 75%

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

Baz

Aly

Abd‐Alla

et al. 2018

Asian J Pharm Clin Res

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Objective: The aim of the present study is to investigate the effect of Morus alba (MA) and Morus rubra L. (MR) fruit extract on obesity-induced cardiac dysfunction and fibrosis in cardiac tissue.Methods: Seventy male Wistar albino rats were randomly divided into five groups of ten rats each. MA and MR have been administered for 6 weeks in obese rats induced by high-fat diet (HFD). Adiponectin, glucagon, troponin, plasminogen activator inhibitor, cell adhesion molecules-1 (intracellular and vascular respectively), C-reactive protein, collagen type II and collagen alpha-1 (III) chain, and lipoxygenase activity were also estimated in serum of obese rats. Histopathological investigation of cardiac tissue was carried out.Results: MA and MR treatments significantly normalized cardiac dysfunction biomarkers as well as cardiac fibrosis as examined by histopathological examination with higher percentage of improvement for MR extract. Conclusion:Hence, it could be concluded that MA and MR extracts have useful effects on obesity-associated cardiac diseases through lipid metabolism regulation, cardiac functions and reversed cardiac fibrosis.

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Section: Discussionsupporting

confidence: 75%

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

Baz

Aly

Abd‐Alla

et al. 2018

Asian J Pharm Clin Res

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“…However, evidence against the anti-obesity role of IL-6 during HFD feeding has been reported. Our group showed a significantly more pronounced increase in body weight in wild-type (WT) mice in contrast to IL-6 −/− mice [ 36 ]. However, Sadagurski et al created transgenic mice with sustained expression of human IL-6 and found that human IL-6 prevents body weight gain during HFD feeding [ 33 ].…”

Section: The Role Of Il-6 In Lipid Metabolismmentioning

confidence: 99%

“…Furthermore, Gregorio et al failed to detect late-onset obesity or disturbed lipid metabolism in IL-6 −/− mice reported by Wallenius et al [ 37 ]. Although it remains unclear, it is suggested that mice age, genetic background, strain specificity, potentially different environmental or dietary factors are likely to contribute to the discrepancy [ 36 ]. In addition, loss of body weight as well as decreased adiposity are usually late-stage symptoms caused by type 2 diabetes.…”

Section: The Role Of Il-6 In Lipid Metabolismmentioning

confidence: 99%

“…Since serum FA concentration is one of the major determinants of cardiac FA uptake rate [ 49 ], dyslipidemia secondary to IL-6 abnormality is likely to facilitate excessive FA import which may result in myocardial lipid accumulation and lipotoxicity. Our group noticed that IL-6 deficiency leads to increased levels of circulating TG and total cholesterol in female mice when fed an HFD [ 36 ]. Moreover, long-term administration of humanized anti-IL-6 antibody Actemra (tocilizumab) results in hypertriglyceridemia in human subjects and the severity appears to increase in a time-dependent manner [ 28 ].…”

Section: The Role Of Il-6 In Cardiac Lipotoxicitymentioning

confidence: 99%

“…Enhanced cardiac expression of FAT/CD36 was observed in IL-6 −/− mice with associated accumulation of biologically active lipids including FFA, DAG, and ceramide [ 54 ]. Our group also noticed that cardiac FAT/CD36 mRNA levels increase during HFD-induced obesity in both WT and IL-6 −/− mice [ 36 ]. However, the elevation is significantly more pronounced in IL-6 −/− mice, suggesting that IL-6 deficiency enhances FAT/CD36 expression.…”

Section: The Role Of Il-6 In Cardiac Lipotoxicitymentioning

confidence: 99%

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IL-6: A Potential Role in Cardiac Metabolic Homeostasis

Zhang

2018

IJMS

Self Cite

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Interleukin-6 (IL-6) is implicated in multiple biological functions including immunity, neural development, and haematopoiesis. Recently, mounting evidence indicates that IL-6 plays a key role in metabolism, especially lipid metabolic homeostasis. A working heart requires a high and constant energy input which is largely generated by fatty acid (FA) β-oxidation. Under pathological conditions, the precise balance between cardiac FA uptake and metabolism is perturbed so that excessive FA is accumulated, thereby predisposing to myocardial dysfunction (cardiac lipotoxicity). In this review, we summarize the current evidence that suggests the involvement of IL-6 in lipid metabolism. Cardiac metabolic features and consequences of myocardial lipotoxicity are also briefly analyzed. Finally, the roles of IL-6 in cardiac FA uptake (i.e., serum lipid profile and myocardial FA transporters) and FA metabolism (namely, β-oxidation, mitochondrial function, biogenesis, and FA de novo synthesis) are discussed. Overall, understanding how IL-6 transmits signals to affect lipid metabolism in the heart might allow for development of better clinical therapies for obesity-associated cardiac lipotoxicity.

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Genetic deletion of IL‐6 increases CK‐MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise

Rovina

Pinto

Muñoz

et al. 2022

Cell Biochemistry & Function

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The intensity, duration, type of contraction, and muscle damage influence interleukin-6 (IL-6) response to acute exercise. However, in response to an exhaustive exercise session, the upregulation of IL-6 in the serum and heart is associated with an inflammatory condition and can inhibit autophagy. This study aimed to investigate the role of IL-6 in autophagy pathway responses and mitochondrial function in the heart of mice submitted to acute exhaustive physical exercise. The mice were allocated into three groups, five animals per group, for the wild type (WT) and the IL-6 knockout (IL-6 KO): Basal (sedentary; Basal), 1 h (after 1 h of the acute exercise; 1 h), and 3 h (after 3 h of the acute exercise; 3 h). After the specific time for each group, the blood was collected, each mouse heart was removed, and the left ventricle (LV) was isolated. In summary, under basal conditions, without the influence of the acute exercise, the IL-6 KO group showed lower number of nuclei in the cardiac tissue, but higher collagen deposition; lower messenger RNA (mRNA) levels of Prkaa1 and Mtco1, but higher mRNA levels of Ulk1; and higher protein levels of the ratio p-AMPK/AMPK in the heart when compared to WT at the same time point. After the acute exercise (1 and 3 h), the IL-6 KO group had lower mRNA levels of Tfam, Mtnd1, Mtco1, and Nampt in the heart when compared to WT after exercise; higher serum levels of creatine kinase (CK), CK-MB, and lactate dehydrogenase for the IL-6 group when compared to the WT group after the exercise. Specifically, the heat-shock protein 60 protein levels in the heart increased 3 h after exhaustive exercise in the WT group, but not in the IL-6 KO group. The study emphasizes that IL-6 may offer cardioprotective effects, including mitochondrial adaptations in response to acute exhaustive exercise.

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Interleukin-6 deficiency facilitates myocardial dysfunction during high fat diet-induced obesity by promoting lipotoxicity and inflammation

Abstract: Our results suggest that IL-6 contributes to limit lipid metabolic disorder, cardiac hypertrophy, fibrosis, inflammation and myocardium lipotoxicity during HFD-induced obesity.

Cited by 30 publications

References 64 publications

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

Therapeutic Impact of Berries (Morus Alba and Morus Rubra) Fruit Extract in the Regression of High-Fat Diet-Induced Cardiac Dysfunction in Rats

IL-6: A Potential Role in Cardiac Metabolic Homeostasis

Genetic deletion of IL‐6 increases CK‐MB, a classic cardiac damage marker, and decreases UPRmt genes after exhaustive exercise

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